Endocrine Abstracts

Section 1: Case history: A 30-year-old Romanian male presented to A&E with symptomatic hypoglycaemia (point-of-care venous glucose 1.8 mmol/l, laboratory value 2.0). He reported 2 days of intermittent left-sided abdominal pain and frequent food craving. Despite eating, he developed dysarthria, hyperhidrosis, somnolence and asthenia, associated with epigastric pain and vomiting. He was recently diagnosed with hepatitis C, discovered incidentally during investigations for chest pain with associated lactataemia. Throughout childhood, he had multiple hospital admissions due to protracted vomiting during intercurrent illness. On one-such occasion, he recalled being hypoglycaemic and requiring intravenous glucose. These episodes persisted into adulthood, and he had identified a maximum fasting period of 15 hours, with symptoms readily responsive to glucose but not fruit. He denied recent alcohol intake. On examination, he was pale, waxy, tachycardic and hypertensive with no other abnormal signs.

Section 2: Investigations: Emergency room investigations showed a severe lactic acidosis (lactate 18 mmol/l, pH 6.9) and marked leucocytosis (neutrophils 17 × 10⁹/l) with a normal CRP. He was hyperkalaemic (6.5 mmol/l), without concurrent acute kidney injury. Liver function testing demonstrated an acutely elevated ALT (163 unit/l), with normal bilirubin and synthetic function. No infective focus was found on bacteriology specimens (blood, urine) or imaging (CT abdomen/pelvis) and toxicology screen was negative. Due to persistent acidosis and hyperkalaemia despite intravenous crystalloid and dextrose therapy, he required haemofiltration, following which he remained euglycaemic without intravenous dextrose.

Section 3: Results and treatment: He was referred to our unit and underwent a supervised fast, developing symptomatic hypoglycaemia after 18 hours. His serum glucose was 1.1 mmol/l with low insulin (<1 mU/l) and C-peptide (50 pmol/l). He had significant ketosis, as well as elevated free fatty acids (3.16 mmol/l), urate (645 µmol/l) and lactate (10.4 mmol/l). A clinical diagnosis of fructose-1,6-bisphosphatase deficiency was made and he was referred for genetic analysis and expert inherited metabolic disorders (IMD) advice. A homozygous sequence variant in fructose-1,6-bisphosphatase (FBP1) gene, previously unreported, was identified. Functional studies are ongoing; however, this is predicted to be pathological.

Section 4: Conclusions and points for discussion: FBP1 deficiency, a key gluconeogenesis enzyme, is a rare autosomal recessive disorder that commonly presents acutely in early childhood when glycogen stores are limited or exhausted. We speculate that a reduced glycogen reserve consequent upon recently diagnosed hepatitis C precipitated this presentation. Given that around 30% of patients referred to the IMD service are diagnosed in adulthood, this represents an important differential in patients presenting with hypoglycaemia and lactic acidosis.